Serum Copper Level and the Copper-to-Zinc Ratio Could Be Useful in the Prediction of Lung Cancer and Its Prognosis: A Case-Control Study in Northeast China

Wang, Wenjun; Xu, Wenrong; Luo, Jingjing; Chen, Xiao; Ma, Kewei; He, Hua; Li, Wei; Cui, Jiuwei

doi:10.1080/01635581.2020.1817957

Cited by 43 publications

(39 citation statements)

References 43 publications

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“…Additionally, Cu and Zn have specific and different activities. Cu is mainly involved in redox homeostasis and inflammatory processes, while Zn maintains cell replication, growth, and repair as well as nucleic acid metabolism and proper immune function [ 35 ]. Therefore, an increased circulating Cu:Zn ratio has been linked with homeostasis breakdown toward systemic inflammation, and was even proposed as an independent biomarker of this phenomenon [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

“…This is in agreement with results presented in this study, where lung cancer patients did not differ from control subjects in terms of Cu and Zn intake. As circulating Cu:Zn ratio increased significantly in advanced stages [ 34 , 35 , 40 ], this biomarker may be a reliable prognostic factor for mortality in neoplasms, including lung cancer. Indeed, our further analysis indicated that the serum Cu:Zn ratio is a good prognostic marker of all-cause mortality in lung cancer, indicating that elevated serum Cu:Zn per 0.1 mg/L increases the risk of all-cause death by 6%, and increased serum Cu concentration per 0.1 mg/L by 13%.…”

Section: Discussionmentioning

confidence: 99%

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Serum and Whole Blood Cu and Zn Status in Predicting Mortality in Lung Cancer Patients

et al. 2020

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Alterations in circulating Cu and Zn are negative predictors of survival in neoplastic patients and are known during lung cancer. However, no data on predicting mortality of lung cancer patients based on the level of these elements in the blood have been presented to date. The aims of this prospective cohort study were as follows: (i) To evaluate the disturbances in serum and whole blood Cu and Zn, (ii) to assess the relationships between serum and whole blood Cu and Zn status and clinical, sociodemographic, and nutritional data, and (iii) to investigate the association of Cu and Zn status with all-cause mortality in lung cancer. Naïve-treatment lung cancer patients (n = 167) were characterized in terms of sociodemographic, clinical, and anthropometric data and dietary intake and compared with sex-matched control subjects (n = 48). Whole blood and serum Cu and Zn status was determined by atomic absorption spectrometry. Cox proportional hazards models adjusted for multiple confounders/mediators were used to estimate the association between all-cause death and Cu and Zn status. Sex, cardiovascular disease, chronic obstructive pulmonary disease, clinical stage, and hemoglobin, platelet, and glucose concentrations significantly differentiated Cu and Zn status. All-cause mortality in lung cancer patients was positively associated with serum Cu levels, Cu:Zn ratio, and whole blood Zn levels. However, an advanced clinical stage of disease was the strongest predictor of all-cause mortality. Circulatory status of Cu and Zn might be included in routine clinical characteristics of patients with lung cancer patients as additional prognostic variables, but only after further more detail studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Serum and Whole Blood Cu and Zn Status in Predicting Mortality in Lung Cancer Patients

et al. 2020

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“…Similar to Cu levels, the ratio of serum Cu/Zn levels was also significantly higher in cancer patients compared to healthy controls, which typically resulted from the increase of Cu levels with simultaneous decrease of Zn levels. Recently, several studies aimed to determine whether circulating Cu levels in serum and full blood, and the ratio of Cu/Zn levels can serve as predictors of the patients’ mortality [ 32 , 33 , 34 , 35 ]. It was demonstrated that higher serum Cu levels, as well as Cu/Zn ratio, were associated with increased all-cause mortality in lung cancer patients [ 32 ].…”

Section: Systemic Changes In Cu Homeostasis Of Cancer Patientsmentioning

confidence: 99%

“…It was demonstrated that higher serum Cu levels, as well as Cu/Zn ratio, were associated with increased all-cause mortality in lung cancer patients [ 32 ]. This might be associated with the increase of Cu levels and Cu/Zn ratio at advanced stages of the disease, as well as during metastatic progression, thus resulting in lowered survivability [ 32 , 33 , 34 , 35 ]. It was suggested that elevation of serum/blood Cu levels might be a consequence of Cu ions release from necrotic tumor tissues [ 36 ] or a result of an inflammatory condition [ 37 , 38 ].…”

Section: Systemic Changes In Cu Homeostasis Of Cancer Patientsmentioning

confidence: 99%

Modulation of Intracellular Copper Levels as the Mechanism of Action of Anticancer Copper Complexes: Clinical Relevance

2021

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Copper (Cu) is a vital element required for cellular growth and development; however, even slight changes in its homeostasis might lead to severe toxicity and deleterious medical conditions. Cancer patients are typically associated with higher Cu content in serum and tumor tissues, indicating increased demand of cancer cells for this micronutrient. Cu is known to readily cycle between the +1 and +2 oxidation state in biological systems. The mechanism of action of Cu complexes is typically based on their redox activity and induction of reactive oxygen species (ROS), leading to deadly oxidative stress. However, there are a number of other biomolecular mechanisms beyond ROS generation that contribute to the activity of anticancer Cu drug candidates. In this review, we discuss how interfering with intracellular Cu balance via either diet modification or addition of inorganic Cu supplements or Cu-modulating compounds affects tumor development, progression, and sensitivity to treatment modalities. We aim to provide the rationale for the use of Cu-depleting and Cu-overloading conditions to generate the best possible patient outcome with minimal toxicity. We also discuss the advantages of the use of pre-formed Cu complexes, such as Cu-(bis)thiosemicarbazones or Cu-N-heterocyclic thiosemicarbazones, in comparison with the in situ formed Cu complexes with metal-binding ligands. In this review, we summarize available clinical and mechanistic data on clinically relevant anticancer drug candidates, including Cu supplements, Cu chelators, Cu ionophores, and Cu complexes.

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“…The proper level of this element determines the activity of antioxidant enzymes, including zinc–copper superoxide dismutase, and it is thanks to its presence that damage to purine bases in DNA, which is considered one of the causes of cancer, is avoided [ 16 , 17 , 18 ]. A higher Cu/Zn ratio contributes to the development of non-small-cell lung cancer [ 19 ]. Due to the aforementioned properties of zinc, it was selected for syntheses with medically active ligands such as benzimidazoles.…”

Section: Introductionmentioning

confidence: 99%

Zinc Coordination Compounds with Benzimidazole Derivatives: Synthesis, Structure, Antimicrobial Activity and Potential Anticancer Application

Raducka

Świątkowski

Korona-Głowniak

et al. 2022

IJMS

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Developing new, smart drugs with the anticancer activity is crucial, especially for cancers, which cause the highest mortality in humans. In this paper we describe a series of coordination compounds with the element of health, zinc, and bioactive ligands, benzimidazole derivatives. By way of synthesis we have obtained four compounds named C1, C2, C4 and C4. Analytical analyses (elemental analysis (EA), flame atomic absorption spectrometry (FAAS)), spectroscopic (Fourier transform infrared spectroscopy (FT-IR), mass spectrometry (MS)) and thermogravimetric (TG) methods and the definition of crystal structures were used to explore the nature of bonding and to elucidate the chemical structures. The collected analytical data allowed the determination of the stoichiometry in coordination compounds, thermal stability, crystal structure and way of bonding. The cytotoxicity effect of the new compounds as a potential antitumor agent on the glioblastoma (T98G), neuroblastoma (SK-N-AS) and lung adenocarcinoma (A549) cell lines and human normal skin fibroblasts (CCD-1059Sk) was also determined. Cell viability was determined by the MTT assay. The results obtained confirmed that conversion of ligands into the respective metal complexes significantly improved their anticancer properties. The complexes were screened for antibacterial and antifungal activities. The ADME technique was used to determine the physicochemical and biological properties.

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Serum Copper Level and the Copper-to-Zinc Ratio Could Be Useful in the Prediction of Lung Cancer and Its Prognosis: A Case-Control Study in Northeast China

Cited by 43 publications

References 43 publications

Serum and Whole Blood Cu and Zn Status in Predicting Mortality in Lung Cancer Patients

Serum and Whole Blood Cu and Zn Status in Predicting Mortality in Lung Cancer Patients

Modulation of Intracellular Copper Levels as the Mechanism of Action of Anticancer Copper Complexes: Clinical Relevance

Zinc Coordination Compounds with Benzimidazole Derivatives: Synthesis, Structure, Antimicrobial Activity and Potential Anticancer Application

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